Multi-site pacing for atrial tachyarrhythmias

ABSTRACT

Tachyarrhythmia is treated by applying anti-tachycardia pacing through at least one multi-site electrode set located on, in or around the heart. The electrode set is arranged and located such that an electrical activation pattern having a wave-front between substantially flat and concave is generated through a reentrant circuit associated with the tachyarrhythmia. The electrode set may be one of a plurality of predefined, multi-site electrode sets located on, in or around the atria. Alternatively, the electrode set may be formed using at least two selectable electrodes located on, in or around the atria.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of copending U.S. patent applicationSer. No. 11/458,649, filed Jul. 19, 2006, titled “Multi-Site Pacing forAtrial Tachyarrhythmias.”

FIELD OF THE INVENTION

The invention relates generally to cardiac devices and more particularlyto implantable devices having multi-site pacing capability forpreventing and terminating atrial tachyarrhythmias.

BACKGROUND

The physiological mechanisms of atrial tachyarrhythmias are oftensingle, stable, reentrant circuit of very short cycle duration, whichdrives the atria, producing arrhythmic conduction. A reentrant circuitis typically a physical and electrical feedback loop composed of cardiaccells that repeatedly cycle electrical impulses in a tight circle andspin off abnormal impulses that propagate over the heart atrialtachycardia. Such a problem feedback loop or “driver,” may be originatedby a “trigger,” such as an abnormally occurring spontaneousdepolarization of cell membrane in the myocardial tissue. Drivers aretypically very regular, and each trigger can initiate many variations ofthese reentrant pathways. Resulting reentrant circuits can be large orsmall, i.e., a macro reentrant circuit, or instead, a small microreentrant circuit, e.g., less then 1 mm in diameter. These small driverscan even mimic a trigger, although they are really small reentrantcircuits.

A typical cycle duration for such a reentrant circuit is on the order of100-200 milliseconds (ms). This is the equivalent of 600 beats perminute at a 100 ms cycle duration. If there is no such trigger and noresulting reentrant circuit, then tachyarrhythmia conduction will not bethere, i.e., the electrical conduction will be normal intrinsicconduction from an intrinsic rhythm (e.g., normal sinus rhythm).

Reentrant circuits can be further understood in terms of cellular actionpotentials continually propagating around the reentrant circuit at arate considerably faster than the heart's intrinsic rate, provided thatthe reentrant wave front, i.e. the head of the propagation wave front,moves slowly enough that tissue ahead recovers excitability, i.e.,slowly enough that a tail or end of the propagation wave front can form.The spatial extent of unexcitable tissue in this circuit is termed thereentrant wavelength, and is approximated by the product of the head'svelocity and the action potential duration. As long as the wavelength isless than the circuit's perimeter, i.e. the reentrant path length, thehead and tail remain separated by an “excitable gap” of tissue waitingto be stimulated. Termination of anatomic reentry requires eliminationof the excitable gap, which can be achieved by appropriate pacing. Anappropriately timed pacing pulse will initiate action potentials thatpropagate in both directions, colliding with the head and “blocking in”the tail.

In more simplified terms, the reentrant circuit can be thought of as aconduction wave front propagating along a tissue mass of somewhatcircular geometry. This circular conduction will consist of a portion ofrefractory tissue and a portion of excitable tissue. To terminate thecircuit, a pacing stimulus should be provided at the time and locationwhen the tissue just comes out of refractoriness. If this occurs, thepaced stimulation wave front proceeds toward the advancing wave front ofthe circuit, colliding with the wave front and interrupting the circuit.If the pacing stimulus arrives too soon it will be ineffective becausethe tissue will still be in refractoriness. If the stimulus arrives toolate, it will generate wave fronts both towards the advancing wave frontand towards the tail of the circuit. Although one pacing-generated wavefront will collide with the advancing wave front of the reentrantcircuit and will halt is progress, the latter pacing-generated wavefront will act to sustain the reentrant circuit.

Anti-tachycardia pacing (ATP) is a standard treatment option toterminate most reentrant tachycardias. Overdrive pacing techniques tointerrupt or to prevent tachycardias virtually always are performed bypacing from a single-site. Studies, however, have demonstrated thatrapid pacing from a single-site can be proarrhythmic due to productionof conduction abnormalities which may contribute to the onset andmaintenance of atrial tachyarrhythmias.

Recent studies in normal and abnormal atria have demonstrated thatlinear triple site rapid bipolar pacing, compared with single sitebipolar rapid pacing, produces 1) more uniform linear activation wavefronts; 2) shorter right atrial and bi-atrial activation time and fastermean epicardial speed; and 3) velocity vectors with a more uniformmagnitude and direction. It has been suggested that a concave (i.e.,curving inward) wave front creates more rapid depolarization in front ofthe advancing wave front compared with a flat wave front pattern. Thisis because the local excitatory current of the concave wave frontpattern is larger than that of the flat wave front pattern. When thewave front is convex (i.e., curving outward), the wave front travelsmore slowly than the flat wave front, because the local excitatorycurrent is distributed over a larger area in front of the wave frontthan the flat wave front. See Comparative Effects of Single- and LinearTriple-site Rapid Bipolar Pacing on Atrial Activation in Canine Models,Ryu et al., Am J Physiol Heart Circ Physiol, Vol. 289.

SUMMARY

Briefly, and in general terms, the invention is directed to thetreatment of tachyarrhythmia by application of anti-tachycardia pacingthrough at least one multi-site electrode set located on, in or aroundthe heart. The electrode set is arranged and located such that anelectrical activation pattern having a wave-front between substantiallyflat and concave is generated through a reentrant circuit associatedwith the tachyarrhythmia. The electrode set may be one of a plurality ofpredefined, multi-site electrode sets located on, in or around theatria. Alternatively, the electrode set may be formed using at least twoselectable electrodes located on, in or around the atria.

These and other aspects and advantages of the invention will becomeapparent from the following detailed description and the accompanyingdrawings which illustrate by way of example the features of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are schematic representations of an implantable devicein relation to a human heart, viewed from the anterior (FIG. 1A) and theposterior (FIG. 1B);

FIG. 2 is a functional block diagram of the implantable stimulationdevice of FIGS. 1A and 1B;

FIG. 3 is a functional block diagram of an atrial tachyarrhythmiatherapy engine;

FIG. 4 is a process chart related to the application of ATP usingpredefined electrode sets selected from a number of available sets;

FIG. 5 is a schematic of various predefined electrode sets relative to areentrant circuit or driver;

FIG. 6 is a process chart related to the application of ATP usingelectrode sets formed from a number of available electrodes; and

FIG. 7 is a schematic of possible electrode sets formed from an array ofelectrodes relative to a reentrant circuit or driver.

DETAILED DESCRIPTION

The following description is of the best mode presently contemplated forpracticing the invention. This description is not to be taken in alimiting sense but is made merely for the purpose of describing thegeneral principles of the invention. The scope of the invention shouldbe ascertained with reference to the issued claims. In the descriptionof the invention that follows, like numerals or reference designationswill be used to refer to like parts or elements throughout.

This disclosure described systems and methods for deliveringanti-tachycardia pacing (ATP) to treat atrial tachyarrhythmias. Thesystem analyzes input from multiple electrodes on, in or near the leftand right atria for the presence of one or more regularly cyclingreentrant circuits. If cycling reentrant circuits are present, thesystem determines the approximate location of the one or more reentrantcircuits or their associated drivers and selects one or more predefinedmulti-electrode sets, or alternatively forms a multi-site electrode setusing a plurality of the atrial electrodes. The multi-site electrodesets are selected or formed such that when electrically stimulated, theycreate a substantially linear to concave electrical activation wavefront through the cardiac tissue toward the one or more reentrantcircuits or drivers.

The multiple electrodes may be placed relative to the right and leftatria on the epicardial surface, the endocardial surface or acombination of the two surfaces. Electrodes may also be placed relativeto the right and left atria implanted within myocardium. The system usesthe multiple electrodes to sense abnormal activation within one or bothof the atria and the abnormal electrical pathways in cardiac tissue thatdrive atrial tachyarrhythmias. At each electrode, the system sensessignals associated with any reentrant circuits. Based on the timingand/or magnitude of sensed signals, the system selects one or morepredefined multi-site electrode sets, or individual electrodes to formone or more multi-site electrode sets, that produce a desirableactivation wave front, i.e., a substantially linear to concave wavefront, directed toward a reentrant circuit or driver.

The probability of ATP succeeding in terminating atrial tachyarrhythmiais related to the ability of the substantially linear to concaveactivation wave front to arrive at the location of a targeted reentrantcircuit or driver in such a manner that the reentrant circuit ismodified or interrupted. Factors influencing this process may includethe distance of the multi-site electrode sets from the reentrantcircuit, the pacing stimulus energy, and the timing of the pacingstimuli relative to the conduction velocities and refractory periods ofthe myocardium. Thus, there are several parameters that can be optimizedto make ATP suitable for effectively terminating atrial tachyarrhythmia.The exemplary system achieves the ability to apply optimal ATP throughone or more multi-site electrode sets located relative the left andright atria.

Referring now to the drawings and particularly to FIGS. 1A and 1B, thereis shown a stimulation device 10 in electrical communication with apatient's heart 12 by way of four leads 14, 16, 18, and 20 fordelivering one or more of multi-chamber stimulation, anti-tachycardiapacing and shock therapy. The stimulation device 10, which may also bereferred to as a cardiac rhythm management device or an implantablemedical device may function as one or more of a pacing apparatus,cardioverter/defibrillator or cardiac resynchronization device.

With reference to FIG. 1A, to sense atrial cardiac signals and toprovide right atrial chamber stimulation therapy, the stimulation device10 is coupled to an implantable right atrial lead 16, typically havingan atrial tip electrode 22 and an atrial ring electrode 24, whichtypically is implanted in the patient's right atrial appendage.

To sense left atrial and ventricular cardiac signals and to provide leftchamber pacing therapy, the stimulation device 10 is coupled to a“coronary sinus” lead 14 designed for placement in the “coronary sinusregion” via the coronary sinus opening for positioning a distalelectrode adjacent to the left ventricle or additional electrode(s)adjacent to the left atrium. As used herein, the phrase “coronary sinusregion” refers to the vasculature of the left ventricle, including anyportion of the coronary sinus, great cardiac vein, left marginal vein,left posterior ventricular vein, middle cardiac vein, and/or smallcardiac vein or any other cardiac vein accessible by the coronary sinus.

Accordingly, an exemplary coronary sinus lead 14 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using a left ventricular (LV) tip electrode 26 and a LVring electrode 28. Left atrial pacing therapy uses, for example, firstand second left atrial (LA) ring electrodes 30 and 32. Shocking therapycan be performed using at least a left atrial (LA) coil electrode 34.For a description of an exemplary coronary sinus lead, see U.S. Pat. No.7,313,444 to Pianca et al., entitled “A Self-Anchoring Coronary SinusLead” and U.S. Pat. No. 5,466,254 to Helland, entitled “Coronary SinusLead with Atrial Sensing Capability,” which patents are incorporatedherein by reference. Coronary sinus lead 14 may also include a pair ofright atrial (RA) ring electrodes 36 and 38, which may be used toprovide right atrial chamber pacing therapy.

The stimulation device 10 is also shown in electrical communication withthe patient's heart 12 by way of an implantable right ventricular lead18, typically having an right ventricular (RV) tip electrode 40, an RVring electrode 42, an RV coil electrode 44, and a superior vena cava(SVC) coil electrode 46 (also known as a right atrial (RA) coilelectrode). Typically, the right ventricular lead 18 is transvenouslyinserted into the heart 12 so as to place the right ventricular tipelectrode 40 in the right ventricular apex so that the RV coil electrode44 will be positioned in the right ventricle and the SVC coil electrode46 will be positioned in the superior vena cava. Accordingly, the rightventricular lead 18 is capable of receiving cardiac signals, anddelivering stimulation in the form of pacing and shock therapy to theright ventricle.

With reference to FIG. 1B, an implantable atrial lead system 20 couplesthe stimulation device 10 to multiple electrodes 48 placed epicardiallyrelative to the left atrium and the right atrium. Although shownschematically as one lead 20, the atrial lead system may be formed oftwo or more separate leads each coupling the stimulation device 10 tothe electrodes 48. The electrodes 48 may have any of severalconfigurations. For example, they may be ring electrodes located on atubular portion of the lead body or hemispherical electrodes carried bya patch. The electrodes 48 are closely spaced such that the stimulationdevice 10 may operate the electrodes as functional pairs, i.e., bipolarmode, or individually, i.e., unipolar mode. During unipolar operation,the reference electrode may be the device case or a coil electrode on anendocardial lead, such as the right atrial SVC coil 46 (FIG. 1A).

The multiple electrodes 48 are typically placed in locations suitablefor both sensing reentrant circuits and applying ATP to terminatetachyarrhythmia conduction. For example, one or more electrodes 48 maybe placed in or around: the area of Bachmann's Bundle 52, the intercavalregion 54, the high right atrium 56, the mid-right atrial free wall 58,the low right atrial free wall 60, the pulmonary veins region 62, theposterior/inferior left atrium region 64, the anterior left atrial freewall 66 and the junction 68 of the left atrial appendage and the leftpulmonary veins.

In order to place the electrodes 48 epicardially in the above-mentionedlocations, the pericardial sac may be entered via a sub-xiphoid approachand the electrodes mapped to sites where reentrant circuits or driversfor sustaining atrial tachyarrhythmia likely originate. In one scenario,an electroanatomical mapping system (e.g., ENSITE, St. Jude Medical,Inc., St. Paul, Minn.) may be used for an accurate placement of theelectrodes 48 on the epicardial surfaces. Placing the electrodes 48epicardially on the left and right atria does not preclude havingelectrodes located on the endocardial surfaces of the atria or insidethe atria or pulmonary veins.

In one configuration, groups of the atrial electrodes 48 formpredefined, multi-site electrode sets 70. For example, the atrialelectrodes 48 may be grouped together in sets of three to provide anumber of triple-site electrode sets. In other configurations, theatrial electrodes 48 may have no predefined association with otherelectrodes and thus may be independently selected to form multi-siteelectrode sets. In either case, individual electrodes 48 or groups ofelectrodes 70, i.e., predefined electrode sets, may be independentlyconnected to the device 10 through separate conductors or daisy chainedtogether. In a daisy-chain configuration, the lead may include anASIC/multiplexer that provides for individualized selection ofelectrodes 48 or electrode sets 70 for sensing and stimulation.

FIG. 2 shows an exemplary block diagram depicting various components ofthe exemplary stimulation device 10. The components are typicallycontained in a case 80, which is often referred to as the “can”,“housing”, “encasing”, or “case electrode”, and may be programmablyselected to act as the return electrode for unipolar operational modes.The case 200 may further be used as a return electrode alone or incombination with one or more of the coil electrodes 34, 44, 46 forstimulating purposes. The case 80 further includes a connector (notshown) having a plurality of terminals (82, 84, 86, 88, 90, 92, 94, 96,98, 100, 102, 104, 106 and 108—shown schematically with the names of theelectrodes to which they are connected shown next to the terminals).Left-heart terminals include: a left ventricular tip terminal (LV TIP)82 for the left ventricular tip electrode 26, a left ventricular ringterminal (LV RING) 84 for the left ventricular ring electrode 28, a leftatrial shocking terminal (LA COIL) 86 for the left atrial coil electrode34, a left atrial ring terminal (LA RING) 88 for the left atrial ringelectrode 30 and a left atrial ring terminal (LA RING) 90 for the leftatrial ring electrode 32;

Right-heart terminals include: a right ventricular tip terminal (RV TIP)92 for the right ventricular tip electrode 40, a right ventricular ringterminal (RV RING) 94 for the right ventricular ring electrode 42, aright ventricular shocking terminal (RV COIL) 96 for the RV coilelectrode 44, a right atrial ring terminal (RA RING) 98 for the atrialring electrode 36, a right atrial ring terminal (RA RING) 100 for theright atrial ring electrode 38, a right atrial tip terminal (RA TIP) 102for the atrial tip electrode 22, a right atrial ring terminal (RA RING)104 for the atrial ring electrode 24 and a SVC shocking terminal (SVCCOIL) 106 for the right atrial SVC coil electrode 46.

Regarding the epicardial atrial electrodes 48, a plurality of atrialpacing terminals (AP1-APn) 108 are provided for independent connectionwith individual electrodes 48 or electrode sets 70. In the case of anASCI/multiplex lead configuration, one pacing terminal 108 may besufficient.

An exemplary stimulation device 10 may include a programmablemicrocontroller 110 that controls various operations of the stimulationdevice, including cardiovascular monitoring, hemodynamic monitoring, andcardiovascular stimulation therapy. Microcontroller 110 includes amicroprocessor (or equivalent control circuitry), RAM and/or ROM memory,logic and timing circuitry, state machine circuitry, and I/O circuitry.

The exemplary stimulation device 10 may further include an atrial pulsegenerator 112 and a ventricular pulse generator 114 that generate pacingstimulation pulses for delivery by the right atrial lead 16, thecoronary sinus lead 14, the right ventricular lead 18 and/or the atriallead system 20 via an electrode configuration switch 116. The electrodeconfiguration switch 116 may include multiple switches for connectingthe desired electrodes to the appropriate I/O circuits, therebyproviding complete electrode programmability. Accordingly, switch 216,in response to a control signal 118 from the microcontroller 110,determines the polarity of the stimulation pulses (e.g., unipolar,bipolar, etc.) by selectively closing the appropriate combination ofswitches.

To provide stimulation therapy in each of the four chambers of theheart, the atrial and ventricular pulse generators 112 and 114 mayinclude dedicated, independent pulse generators, multiplexed pulsegenerators, or shared pulse generators. The pulse generators 112 and 114are controlled by the microcontroller 110 via appropriate controlsignals 120 and 122, respectively, to trigger or inhibit the stimulationpulses.

Microcontroller 110 is illustrated as including timing control circuitry124 to control the timing of the stimulation pulses (e.g., pacing rate,atrioventricular (AV) delay, atrial interconduction (A-A) delay, orventricular interconduction (V-V) delay, native atrial event to nativeor stimulated ventricular event (PV) delay, (AV/PV) delay, etc.). Thetiming control circuitry may also be used for the timing of refractoryperiods, blanking intervals, noise detection windows, evoked responsewindows, alert intervals, marker channel timing, and so on.

Microcontroller 110 may also implement an arrhythmia detector 126, amorphology detector 128, and an atrial tachyarrhythmia therapy engine130. The microcontroller 110 may process input from physiologicalsensors 132, such as accelerometers of an activity/position module 134,and a minute ventilation module 136 etc.,

The components 126, 128, 130 may be implemented in hardware as part ofthe microcontroller 110, or as software/firmware instructions programmedinto an implementation of the stimulation device 10 and executed on themicrocontroller 110 during certain modes of operation. Although notshown, the microcontroller 110 may further include other dedicatedcircuitry and/or firmware/software components that assist in monitoringvarious conditions of the patient's heart and managing pacing therapies.

Atrial sensing circuits 138 and ventricular sensing circuits 140 mayalso be selectively coupled to the right atrial lead 16, coronary sinuslead 14, the right ventricular lead 18 and/or the atrial lead system 20through the switch 116 to detect the presence of cardiac activity withrespect to each of the four chambers of the heart. The sensing circuits138 and 140 may include dedicated sense amplifiers, multiplexedamplifiers, or shared amplifiers. Switch 116 determines the “sensingpolarity” of the cardiac signal by selectively closing the appropriateswitches. In this way, the clinician may program the sensing polarityindependent of the stimulation polarity.

Each sensing circuit 138 and 140 may employ one or more low powerprecision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit toselectively sense the cardiac signal of interest. The automatic gaincontrol enables the exemplary stimulation device 10 to sense lowamplitude signal characteristics of atrial or ventricular fibrillation.

The outputs of the atrial and ventricular sensing circuits 138 and 140are connected to the microcontroller 110 which, in turn, is able totrigger or inhibit the atrial and ventricular pulse generators 112 and114 in a demand fashion in response to the absence or presence ofcardiac activity in the appropriate chambers of the heart. The sensingcircuits 138 and 140 receive control signals from the microcontroller110 over signal lines 142 and 144 to control, for example, the gainand/or threshold of polarization charge removal circuitry (not shown)and the timing of blocking circuitry (not shown) optionally coupled tothe inputs of the sensing circuits 138, 140.

Cardiac signals are supplied to an analog-to-digital (ND) dataacquisition system 146, which is configured to acquire intracardiacelectrogram signals, convert the raw analog data into a digital signal,and store the digital signals for later processing and/or telemetrictransmission to an external device 148. The data acquisition system 146is coupled to the right atrial lead 16, the coronary sinus lead 14, theright ventricular lead 18 and the atrial lead system 20 through theswitch 116 to sample cardiac signals across any pair of desiredelectrodes.

The data acquisition system 146 is coupled to the microcontroller 110,or other detection circuitry, to assist in detecting an evoked responsefrom the heart 12 in response to an applied stimulus, which is oftenreferred to as detecting “capture”. Capture occurs when an electricalstimulus applied to the heart is of sufficient energy to depolarize thecardiac tissue, thereby causing the heart muscle to contract. Themicrocontroller 110 detects a depolarization signal during a windowfollowing a stimulation pulse, the presence of which indicates thatcapture has occurred. The microcontroller 110 enables capture detectionby triggering the ventricular pulse generator 114 to generate astimulation pulse, starting a capture detection window using the timingcontrol circuitry 124 within the microcontroller 110, and enabling thedata acquisition system 146 via control signal 150 to sample the cardiacsignal that falls in the capture detection window and, based on theamplitude, determines if capture has occurred.

The microcontroller 110 is further coupled to a memory 152 by a suitabledata/address bus 154. The programmable operating parameters used by themicrocontroller 110 are stored in memory 152 and used to customize theoperation of the exemplary stimulation device 10 to suit the needs of aparticular patient. Such operating parameters define, for example,pacing pulse amplitude, pulse duration, electrode polarity, rate,sensitivity, automatic features, arrhythmia detection criteria, and theamplitude, wave shape and vector of each shocking pulse to be deliveredto the patient's heart 12 within each respective tier of therapy.

The operating parameters of the exemplary stimulation device 10 may benon-invasively programmed into the memory 152 through a telemetrycircuit 156 in telemetric communication via communication link 158 withthe external device 148, such as a programmer, local transceiver, or adiagnostic system analyzer. The microcontroller 110 can activate thetelemetry circuit 156 with a control signal 160. The telemetry circuit156 allows intracardiac electrograms and status information relating tothe operation of the exemplary stimulation device 10 (as contained inthe microcontroller 110 or memory 152) to be sent to the external device148 through an established communication link 158.

The physiological sensors 132 referred to above can further include, forexample, “rate-responsive” sensors that adjust pacing stimulation ratesaccording to the exercise state of the patient. Accordingly, themicrocontroller 110 responds by adjusting the various pacing parameters(such as rate, AV Delay, V-V Delay, etc.) at which the atrial andventricular pulse generators 112 and 114 generate stimulation pulses.

The physiological sensors 132 may include mechanisms and sensors todetect bodily movement 134, minute ventilation 136, changes in bloodpressure, changes in cardiac output, changes in the physiologicalcondition of the heart, diurnal changes in activity (e.g., detectingsleep and wake states), G-force acceleration of the ICD case 200,duration of the cardiac QT interval, blood oxygen saturation, blood pH,changes in temperature, respiration rate, and QRS wave duration. Whileshown as being included within the exemplary stimulation device 10, thephysiological sensor(s) 132 may also be external to the exemplarystimulation device, yet still be implanted within or carried by thepatient, e.g., a blood pressure probe. Examples of physiological sensorsexternal to the case 80 that may be deployed by stimulation device 10include sensors that, for example, sense respiration activities, O2saturation, evoked response, pH of blood, and so forth.

The illustrated physiological sensors 132 include one or moreactivity/position sensors 134 (e.g., 1D or 3D accelerometers, movementsensors, etc.) to detect changes in the patient's position. Theactivity/position sensors 134 can be used to assist detection oforthostatic hypotension caused by transition from a less upright postureto a comparatively more upright posture. One example postural changeleading to orthostatic hypotension in susceptible individuals is amovement from a supine position in a rest state (e.g., sleeping in bed)to an upright position in a non-rest state (e.g., sitting or standingup).

In one configuration, accelerometer output signal is bandpass-filtered,rectified, and integrated at regular timed intervals. A processedaccelerometer signal can be used as a raw activity signal. The devicederives an activity measurement based on the raw activity signal atintervals timed according to the cardiac cycle. The activity signalalone can be used to indicate whether a patient is active or resting.The activity measurement can further be used to determine an activityvariance parameter. A large activity variance signal is indicative of aprolonged exercise state. Low activity and activity variance signals areindicative of a prolonged resting or inactivity state.

The minute ventilation (MV) sensor 136 may also be included in thephysiological sensors 132 in order to sense rate and depth of breathing.Minute ventilation can be measured as the total volume of air that movesin and out of a patient's lungs in a minute. The MV sensor 136 may usean impedance measuring circuit 162 to sense air movement by measuringimpedance across the chest cavity.

The impedance measuring circuit 162 is enabled by the microcontroller110 via a control signal 164 and can be used for many things besides theabovementioned detection of air movement in and out of the lungs,including: lead impedance surveillance during acute and chronic phasesfor proper lead positioning or dislodgement; detecting operableelectrodes and automatically switching to an operable pair ifdislodgement occurs; measuring respiration or minute ventilation;measuring thoracic impedance for determining shock thresholds; detectingwhen the device has been implanted; measuring cardiac stroke volume;detecting the opening of heart valves; and so forth. The impedancemeasuring circuit 162 may be coupled to the switch 116 so that anydesired electrode may be used.

The exemplary stimulation device 10 additionally includes a battery 164that provides operating power to all of the components shown in FIG. 2.The battery 164 is capable of operating at low current drains for longperiods of time, e.g., less than 10 μA, and is capable of providinghigh-current pulses for capacitor charging when the patient requires ashock pulse (e.g., in excess of 2 A, at voltages above 2 V, for periodsof 10 seconds or more). The battery 164 also desirably has predictabledischarge characteristics so that elective replacement time can bedetected. As one example, the exemplary stimulation device 10 employslithium/silver vanadium oxide batteries.

The exemplary stimulation device 10 can further include magnet detectioncircuitry (not shown), coupled to the microcontroller 110, to detectwhen a magnet is placed over the exemplary stimulation device. A magnetmay be used by a clinician to perform various test functions of theexemplary stimulation device 10 and/or to signal the microcontroller 110that an external programmer 148 is in place to receive or transmit datato the microcontroller through the telemetry circuits 156.

The microcontroller 110 further controls a shocking circuit 166 via acontrol signal 168. The shocking circuit 166 generates shocking pulsesof low (e.g., up to 0.5 joules), moderate (e.g., 0.5-10 joules), or highenergy (e.g., 11-40 joules), as selected by the microcontroller 110.Such shocking pulses are applied to the patient's heart 12 through atleast two shocking electrodes selected, for example, from the leftatrial coil electrode 122, the RV coil electrode 132, and/or the SVCcoil electrode 134. As noted above, the case 80 may act as an activeelectrode in combination with the RV coil electrode 132, or as part of asplit electrical vector using the SVC coil electrode 134 or the leftatrial coil electrode 122 (i.e., using the RV coil electrode 132 as acommon electrode).

Cardioversion shocks are generally considered to be of low to moderateenergy level so as to minimize pain felt by the patient, and/orsynchronized with an R-wave and pertain to the treatment of tachycardia.Defibrillation shocks are generally of moderate to high energy level,corresponding to thresholds in the range of 5-40 joules, deliveredasynchronously (since R-waves may be too disorganized), and pertainexclusively to the treatment of fibrillation. Accordingly, themicrocontroller 110 is capable of controlling the synchronous orasynchronous delivery of the shocking pulses.

With reference to FIG. 3, the atrial tachycardia therapy engine 130portion of the microcontroller 110 (FIG. 2) includes a pacing parametersoptimizer 170 and an atrial ATP optimizer 172. In general, the atrialoptimizer 172 provides pacing techniques to increase the efficacy ofatrial tachyarrhythmias termination using the atrial electrodes 48. Byanalyzing atrial activation patterns during atrial tachyarrhythmia fromelectrograms of each electrode 48 site, the atrial optimizer 172 candetermine the presence of a reentrant circuit and if such a circuit ispresent, which predefined or formed atrial electrodes set(s) 70 wouldproduce the desired activation wave through the reentrant circuit. Theatrial optimizer 172 may also determine ATP timing parameters.

The pacing parameters optimizer 170 works with the atrial optimizer 172to compute the more ancillary pacing parameters to be used during ATP.The pacing parameters optimizer 170 can determine the number of thepacing stimuli to apply, the pulse width, the various time intervalsbetween the pacing stimuli, etc. Typically, the pacing duration, thepacing threshold, the pacing rate; as well as the pulse width, the pulseshape, and the pulse interval optimize ATP parameters to minimizediscomfort to patients, power consumption of the device, and also toreduce proarrhythmic effects of pacing. Thus, the optimal number ofstimuli and typically a relatively lower pacing threshold will beselected as a part of the optimization process. The atrialtachyarrhythmia therapy engine 130 then uses all the parameters todeliver ATP in a manner that efficiently terminates atrialtachyarrhythmia.

The atrial optimizer 172 includes an atrial multi-electrode manager 174,an initial pacing cycle calculator 176, an excitable gap windowcalculator 178 and an electrode mapper 180. The atrial multi-electrodemanager 174 portion of the atrial optimizer 172 includes a sensingdivision 182 and an ATP delivery division 184.

The sensing division or reentrant detector 182 detects the presence of areentrant circuit in relation to electrode sites based on atrialactivation patterns. Using the multiple electrodes implanted relativethe atria, each electrode becomes a site for listening for the regular,relatively high frequency cycling of a reentrant circuit, or thetachyarrhythmic conduction being propagated from such a circuit. If onlyone reentrant circuit is active, then each electrode may sense aslightly different amplitude of the cyclical conduction and at aslightly different time, depending on distance of a particular electrodefrom the physical position of the reentrant circuit. If more than onereentrant circuit is active, then different electrodes may sensedifferent frequencies and amplitudes of cycling. Details on one possiblereentrant circuit or driver location process are included in U.S. patentapplication Ser. No. 11/458,655, filed Jul. 19, 2006, titled “System andRelated Methods for Identifying a Fibrillation Driver,” the disclosureof which is hereby incorporated by reference.

If the presence of a reentrant circuit has been detected by thereentrant detector 182, the atrial electrode mapper 180 identifies thepositions of the atrial electrodes 48 with respect to the reentrantcircuit based on the respective timings of signals sensed at eachrespective electrode. Using this temporal data and known positioning ofthe electrodes 48 with respect to each other, the electrode mapper 180identifies one or more predefined multi-site electrode sets 70 capableof providing the desired activation wave front, or two or moreindividual electrodes that form a multi-site electrode set capable ofproviding the desired activation wave front.

In one implementation, ATP is applied one multi-site electrode set at atime, beginning at the electrode set that will deliver the desiredactivation wave front, which is closest to the reentrant circuit. If ATPapplied at this electrode set fails to terminate the atrialtachyarrhythmia, then the multi-electrode manager 174 progresses to thenext closest electrode set capable of delivering the desired activationwave front, and so on.

If atrial tachyarrhythmia persists, then ATP may be delivered usingmultiple multi-site electrode sets. In on such implementation, the ATPdelivery engine 184 applies each pulse of the ATP in a syncopated manneracross multiple multi-site electrode sets, so that each ATP pulse issequentially applied in synchronization with the excitable gap as itpasses each electrode in turn.

If the syncopated application of ATP just described fails to end theatrial tachyarrhythmia, then as a next option the ATP delivery engine184 applies ATP simultaneously at multiple selected multi-site electrodesets or at all the available multi-site electrode sets, perhaps as alast option for ATP treatment of atrial tachyarrhythmia. Thus, theatrial optimizer 172 can apply a hierarchical protocol of increasinglyinvasive ATP applications.

With reference to FIG. 4, an exemplary process for applying ATP usingpredefined multi-site electrode sets 70 includes several operationssummarized in individual blocks. Some operations may be performed inhardware and/or as machine-readable instructions (software or firmware)that can be executed by a processor, such as microcontroller 110. Theexemplary process may be implemented in connection with many suitablyconfigured stimulation devices, although it will be described as beingexecuted by the exemplary atrial tachyarrhythmia therapy engine 130 ofthe exemplary stimulation device 10.

At block B10, the multi-site electrode set that is located closest tothe reentrant circuit or driver is identified. With reference to FIG. 5,such a determination may be made based on the respective timing and/ormagnitude of the signals sensed at the electrodes 48 in the electrodesets 70. For example, given first, second and third triple-siteelectrode sets 70(1), 70(2), 70(3), the first electrode set would beidentified as closest to the driver 200 based on the position ofelectrode 48(1)—it is the closest electrode to the driver.

Continuing with FIG. 4, at block B12, a determination is made as towhether the identified, closest multi-site electrode set is positionedrelative to the driver so as to deliver the desired activation wavefront. Returning to FIG. 5, such a determination may be made based onthe timing and/or magnitude of sensed signals at each of the electrodes48 in the electrode set 70. With respect to the first electrode set70(1), signals from the driver would reach the first electrode 48(1)before the second and third electrodes 48(2), 48(3); while reaching thesecond electrode 48(2) before the third electrode 48(3). From thistiming data, and the known linear arrangement of the predefinedtriple-site electrode set, it may be determined that the positioning ofthe first electrode set 70(1) relative to the driver 200 is notconducive to producing the desired wave front. That is, the activationpattern 202(1) produced by ATP pulses applied through the firstelectrode set 70(1) would not result in a substantially linear toconcave wave front passing through the driver 200. To the contrary, thewave front 202(1) toward the driver 200 that is produced by the firstelectrode set 70(1) would be convex, as if emanating from a singleelectrode 48(1).

Returning to FIG. 4, if it is determined that the identified electrodeset will not produce the desired activation wave front, then at blockB14 it is determined if more multi-set electrode sets are available forATP consideration. If more sets are available, then at block B16, themulti-site electrode set that is located next closest to the reentrantcircuit or driver is identified. The process then returns to block B12to determine if this identified electrode set will produce the desiredactivation wave front.

Returning to the example of FIG. 5, triple-site electrode set 70(2)would be identified as the next closest electrode set based on theposition of electrode 48(5). The sensing of signals from the reentrantcircuit at each of the three electrodes 48(4), 48(5), 48(6) would occurat substantially the same time. Given this timing data, and the knownlinear arrangement of the predefined triple-site electrode sets, it maybe determined that the second electrode set 70(2) could produce thedesired activation wave front. That is, the activation pattern 202(2)produced by applying ATP pacing pulses through the second electrode set70(2) would result in a substantially linear to concave wave frontpassing through the driver 200.

For ease in illustration, the activation patterns 202 shown in FIG. 5are presented in idealized form, wherein the portion of the wave frontdirected toward the driver 200 is smooth, curvilinear and concave. Inpractice, however, it is understood that the wave fronts produced bymulti-site electrode sets will most likely be characterized byundulating, non-smooth patterns which, while not as ideal as those shownin FIG. 5, are considered desirable. Such patterns are shown anddescribed in the previously cited Ryu et al. article, which is herebyincorporated by reference.

Returning to FIG. 4, once a multi-site electrode set capable ofdelivering the desired activation wave front is identified, the process,at block B18, delivers ATP through the identified electrode set. Detailsrelated to the ATP therapy are described below. At block B20, adetermination is made as to whether atrial tachyarrhythmia has beenterminated by the applied ATP. If the tachyarrhythmia has terminated,the process ends. If, however, tachyarrhythmia persists, the processproceeds to block B14 where a determination is made regarding thepresence of additional multi-site electrode sets that have not yet beenconsidered for ATP. If additional electrode sets are present, theprocess proceeds to block B16 where the multi-site electrode set that islocated next closest to the reentrant circuit or driver, and that hasnot yet been considered for ATP is identified. Continuing with theexample of FIG. 5, the third electrode set 70(3) represents such anadditional electrode set.

If at block B14, it is determined that additional multi-site electrodesets are not present, the process proceeds to block B22, where other ATPtherapies may be applied using the present multi-site electrode sets.For example, as a first type of other therapy, ATP may be appliedthrough each of the previously identified multi-site electrode setssimultaneously, sequentially or in a syncopated manner, as describedbelow. As another or additional type of therapy, ATP may be appliedsimultaneously, sequentially or in a syncopated manner through allmulti-site electrode set, regardless of the type of activation wavefront it produces with respect to the driver.

As previously mentioned, instead of being grouped into predefined,multi-site electrode sets, the atrial electrodes 48 may be independentlyselectable to form multi-site electrode sets. For example, withreference to FIG. 1B, the atrial electrodes 48 in the regions of thepulmonary veins 62 may be arranged in a 3×4 array of individuallyselectable electrodes instead of the shown set of three, triple-siteelectrode sets.

With reference to FIG. 6, an exemplary process for forming one or moremulti-site electrode sets from a plurality of available electrodesincludes, at block B30, identifying a core atrial electrode. Anyelectrode may be selected as a core electrode based on some type ofcriteria. For example, a core-electrode selection criterion may be basedon distance from the driver 200, with the electrode closest to thedriver being selected first. With reference to FIG. 7, such adetermination may be made based on the respective timing and/ormagnitude of the signals sensed at the electrodes in the electrode array72. For example, given a 3×4 electrode array positioned relative to adriver 200, electrode X₁ would be identified as closest to the driver.

Returning to FIG. 6, at block B32, one or more additional electrodesadjacent the identified electrode, are selected as a possible electrodefor a multi-site electrode set. For example, with reference to FIG. 7,electrodes adjacent X₁ would include one or both of X₂ and X₅.

Continuing with FIG. 6, at block B34, a determination is made as towhether the formed multi-site electrode set is positioned relative tothe driver so as to deliver the desired activation wave front. Returningto FIG. 7, such a determination may be made based on the timing and/ormagnitude of sensed signals at each of the electrodes in the formedelectrode set. For example, if X₂ was selected, thus forming a dual-siteelectrode set consisting of electrodes X₁ and X₂, signals from thedriver 200 would reach the first electrode X₁ before the secondelectrode X₂. From this timing data, and the known arrangement of theelectrodes in the electrode array 72, it may be determined that theelectrode set 74(1) formed from electrodes X₁ and X₂ is not conducive toproducing the desired wave front. That is, the activation pattern 204(1)produced by ATP pulses applied through the first formed electrode set74(1) would not result in a substantially linear to concave wave frontpassing through the driver 200.

If it is determined that the formed electrode set will not produce thedesired activation wave front, the process proceeds to block B36 where,if available, another electrode adjacent the identified core electrodeis selected to form another electrode set. For example, as shown FIG. 7,electrode X₅ is another electrode that is adjacent X₁. The process thenreturns to B34 where it is determined if the electrode set 74(2) formedby electrodes X₁ and X₅ electrode set will produce the desiredactivation wave front. In this example, like the electrode set 74(1)formed by electrodes X₁ and X₂, the wave front 204(2) produced by theelectrode set 74(2) formed of electrodes X₁ and X₅ will not likelyproduce the desired wave front.

If there are no other electrodes adjacent the identified core electrode,the process proceeds to block B38 where it is determined whether morecore electrodes are available. If another core electrode is available,the process proceeds to block B40 where a new core electrode isselected. For example, if the first core electrode was selected based onbeing closest to the driver, the next core electrode may be selectedbased on being next closest to the driver. In the example array of FIG.7, a possible next core electrode is electrode X₂. Once the next coreelectrode is selected the process returns to block B32 where one or moreadjacent electrodes are selected to form an electrode set with thecurrent core electrode and further processing occurs as previouslydescribed.

With reference to FIG. 7, one possible adjacent electrode for X₂ iselectrode X₅. The activation wave front 204(3) produced by thisdual-site electrode set 74(3) would likely be substantially linear toslightly concave. As with previously described FIG. 5, for ease inillustration, the activation patterns 204 shown in FIG. 7 are presentedin idealized form, wherein the portion of the wave front directed towardthe driver 200 is smooth and linear or flat. In practice, however, it isunderstood that the wave fronts produced by multi-site electrode setswill most likely be characterized by undulating, non-smooth/linear/flatwave front patterns which, while not as ideal as those shown in FIG. 7,are considered desirable.

Returning to FIG. 6, once an electrode set capable of delivering thedesired activation wave front is identified, the process, at block B42,delivers ATP through the formed multi-site electrode set. Detailsrelated to the ATP therapy are described below. At block B44, adetermination is made as to whether atrial tachyarrhythmia has beenterminated by the applied ATP. If the tachyarrhythmia has terminated,the process ends. If, however, tachyarrhythmia persists, the processproceeds to block B36 where processing proceeds as previously described.

If tachyarrhythmia persists, and all possible multi-site electrode setshave been formed with the current core electrode, and no more coreelectrodes are available, the process proceeds to block B46, where otherATP therapies may be applied using one or more of the previously formedmulti-site electrode sets. For example, as a first type of othertherapy, ATP may be applied through each of the previously formedmulti-site electrode sets simultaneously, sequentially or in asyncopated manner, as described below. As other or additional types oftherapy, ATP may be applied simultaneously, sequentially or in asyncopated manner through all multi-site electrode sets, regardless ofthe type of activation wave front it produces with respect to thedriver. As still another therapy, ATP may be applied through all of theindividual, single-site electrodes simultaneously, sequentially or in asyncopated manner.

The pacing of individual electrodes within a multi-site electrode setmay be time controlled in order to produce the desired activation wavefront from a group of electrodes that may not otherwise produce thedesired wave front. For example, returning to FIG. 7, a triple-siteelectrode set may be formed from electrodes X₁, X₂ and X₅. Simultaneousapplication of pacing stimuli to the electrodes would likely produce aconvex activation wave front which is not a desired wave front. If,however, pacing among the electrodes is timed so that pulses aredelivered through adjacent electrodes X₂ and X₅ slightly prior to thepulses delivered through the core electrode X₁, the resulting wave frontwould likely be substantially linear to concave. The offset timing ofthe pacing pulses would most likely correspond to the offset timingnoted during signal sensing at the respective electrodes in the set.

Returning to FIG. 3 and with respect to the application of ATP through asingle multi-site electrode set (e.g. FIG. 4, block B18 and FIG. 5,block B42), once an electrode set has been selected or formed for ATPdelivery, the atrial optimizer 172 and the pacing parameters optimizer170 calculate the timing and other pulse characteristic and deliveryparameters.

Regarding the timing of ATP, the reentrant detector 182 of themulti-electrode manager 174 senses the cycle duration of reentrantcircuits, and more particularly senses the timing of the excitable gapsegment of the reentrant circuit, at the multi-site electrode set. Theexcitable gap window calculator 178 then finds an excitable gap that canbe stimulated to stop an atrial tachyarrhythmia. In one implementation,once the reentrant detector 182 finds the initial reentrant circuitcycle duration, e.g., by sensing intracellular upstroke potentials, thenthe window calculator 178 waits 80-90% of cycle, which typically is thestarting point of the window. The voltage required can be high, e.g., ata current of 20 mA, 7.5-10 volts may be applied for approximately 0.5ms.

The reentrant detector 182 searches for periodic signals at high rates,e.g., 105-107 millisecond cycles (around 10 Hertz), at extremely regularintervals. Unlike regular arrhythmia, these are not typically areas oftachyarrhythmia conduction, but instead are areas, i.e., “sites,” wherea driver exists. ATP is then applied by the ATP delivery engine 184through the multi-site electrode set, at the cycle duration orfrequency.

In one implementation, if atrial tachyarrhythmia persists, the ATPdelivery engine 184 calculates a shorter cycle (i.e., a higherfrequency) at which to apply ATP in subsequent attempts. For example,subsequent rounds of ATP may be applied at 95%, 90%, 85%, etc., of theinitially sensed cycle duration. Relatively large stimuli are used,e.g., up to 100 volts. Thus, if the initial cycle duration is 100 ms or99 ms, then subsequent bursts of ATP might be given at 95 ms, then 90ms, then 85 ms, etc. In one implementation, multiple pulses of ATP areapplied five times through the multi-site electrode set at each cycleduration or frequency. If the atrial tachyarrhythmia stops, then thenext ATP cycle is not applied. In variations, the cycle duration of theapplied ATP is decreased by the ATP delivery engine 184 in 5%, 3%, 2%,or 1% intervals. Again, high voltage may be used if the tissue is notvery excitable.

Regarding the application of ATP through multiple multi-set electrodesets (e.g. FIG. 4, block B22 and FIG. 6, block B46) the ATP deliveryengine 184 paces simultaneously at each of the multi-site electrodesets, at a homogenous refractory period. Simultaneous stimulation mayresynchronize the heart from the spontaneous conduction patterns ofatrial tachyarrhythmias. Applying ATP at multiple multi-site electrodesets at once enables resynchronization of the atrium so that refractoryperiods are homogenized and less likely to have reentrant arrhythmiaspontaneously occur. As refractory periods shrink, the tissue becomesmore susceptible to faster reentrant cycles, but if this is controlledby the ATP delivery engine 184 the refractory periods lengthen, and thelonger they are, the less likely spontaneous reentry will reoccur,because a larger circuit will be required.

The ATP delivery engine 184 may administer a simultaneous pulse at allmulti-site electrode sets at once, delivered at very precise timingduring the excitable gap. In one implementation, the precise timing isachieved merely by beginning stimulation timing at the high end of theexcitable gap and changing the timing by increments until the low end ofthe excitable gap is stimulated. Sometime during this range of differenttimings, the midpoint of the excitable gap is approximated, offeringassurance that the excitable gap has been stimulated directly, or“squarely.”

In another implementation the ATP delivery engine 184 applies the ATP ina syncopated manner, with the cycle durations of the applied ATP pulsesindividualized for each multi-site electrode set, to coincide with theexcitable gap as sensed by the respective multi-site electrode set.Thus, while one multi-site electrode set may be applying ATP at 10 msintervals, another multi-site electrode set may be applying ATP at 92 msintervals. Application of ATP at each multi-site electrode set issynchronized with the cycle duration, as sensed at by one or more of theelectrodes in the respective electrode set.

It will be apparent from the foregoing that while particular forms ofthe invention have been illustrated and described, various modificationscan be made without departing from the spirit and scope of theinvention. For example, predefined electrode sets or individualelectrodes placed in, on or around the ventricles may be used to applymulti-site-electrode-set ATP to terminate ventricular arrhythmias.Consequently, the specific structural and functional details disclosedherein are merely representative and do not limit the scope of theinvention. The scope of the invention should be ascertained withreference to the claims.

What is claimed is:
 1. A method of treating atrial tachyarrhythmia, the method comprising: forming at least one multi-site electrode set including at least two electrodes configured to have pacing stimuli applied thereto and selected from a plurality of electrodes adapted to be positioned on, in or around the atria, wherein the at least one formed electrode set is arranged with respect to a reentrant circuit such that application of individual pacing stimuli to the at least two electrodes within the formed electrode set will generate a desired electrical activation pattern through the reentrant circuit, the desired activation pattern having a wave-front between substantially flat and concave; and applying individual pacing stimuli to each of the at least two electrodes within the at least one formed electrode set.
 2. The method of claim 1, wherein forming at least one multi-site electrode set including at least two electrodes configured to have pacing stimuli applied thereto comprises: designating one of the plurality of electrodes as a core electrode and as one of the at least two electrodes in the electrode set; and selecting at least one electrode adjacent the core electrode as another one of the at least two electrodes in the electrode set.
 3. The method of claim 2, wherein designating a core electrode comprises: sensing signals from the reentrant circuit at each of the plurality of electrodes; and selecting a core electrode based on location relative to the reentrant circuit as indicated by the sensed signals.
 4. The method of claim 3, wherein the electrode closest to the reentrant circuit is selected as the core electrode.
 5. The method of claim 2, further comprising: sensing signals from the reentrant circuit at the core electrode and the at least one adjacent electrode; and determining whether an electrode set formed from the core electrode and the at least one adjacent electrode will generate the desired activation pattern through the reentrant circuit based on the sensed signals and the known location of the electrodes within the electrode set relative to each other and to the reentrant circuit.
 6. The method of claim 5, wherein determining is based on at least one of the timing and magnitude of signals sensed at each electrode within the electrode set.
 7. The method of claim 1, further comprising: if atrial tachyarrhythmia is still present after pacing through the first formed electrode set, forming an alternate electrode set using one or more other electrodes adjacent the core electrode; determining whether the alternate electrode set will generate the desired activation pattern through the reentrant circuit based on signals sensed at the electrodes and the known location of the electrodes within the alternate electrode set relative to each other and to the reentrant circuit; and if the alternate electrode set will generate the desired activation pattern, applying pacing stimuli through the alternate electrode set.
 8. The method of claim 1, further comprising: if atrial tachyarrhythmia is still present after pacing through the first formed electrode set, selecting a new core electrode; forming an alternate electrode set using one or more other electrodes adjacent the new core electrode; determining whether the alternate electrode set will generate the desired activation pattern through the reentrant circuit based on signals sensed at the electrodes and the known location of the electrodes within the alternate multi-site electrode set relative to each other and to the reentrant circuit; and if the alternate electrode set will generate the desired activation pattern, applying pacing stimuli through the alternate formed electrode set.
 9. The method of claim 1, wherein forming an electrode set comprises: determining whether a plurality of formed electrode sets will generate the desired activation pattern through the reentrant circuit; and when a plurality of formed electrode sets will generate the desired activation pattern, selecting at least two of the formed electrode sets and applying pacing stimuli to each of the at least two electrodes within each of the selected formed electrode sets.
 10. The method of claim 9, wherein pacing stimuli is applied to the at least two selected formed electrode sets in one of a simultaneous, sequential or syncopated manner.
 11. The method of claim 1, wherein applying pacing stimuli comprises applying stimuli to each of the at least two electrodes in a formed electrode set substantially simultaneously.
 12. The method of claim 1, wherein applying pacing stimuli comprises applying stimuli to the at least two electrodes in an offset manner corresponding to an offset in the timing of signals sensed at the electrodes.
 13. The method of claim 1, wherein the pacing stimuli comprises anti-tachycardia pacing (ATP) pacing.
 14. A system for treating atrial tachyarrhythmia, the system comprising: a plurality of electrodes adapted to be positioned on, in or around the atria; a pulse generator connected to the electrodes; and a processor operative to: form at least one multi-site electrode set including at least two electrodes selected from the plurality of electrodes and configured to have pacing stimuli applied thereto, wherein the at least one formed electrode set is arranged with respect to a reentrant circuit such that application of individual pacing stimuli to the at least two electrodes within the formed electrode set will generate a desired electrical activation pattern through a reentrant circuit, the desired pattern having a wave-front between substantially flat and concave; and control the pulse generator to apply individual pacing stimuli to each of the at least two electrodes within the at least one formed electrode set.
 15. The system of claim 14, wherein at least some of the electrodes are adapted to be positioned on the atria relative to the epicardial surface.
 16. The system of claim 14, wherein at least some of the electrodes are adapted to be positioned in the atria relative to the endocardial surface.
 17. The system of claim 14, wherein the electrodes are adapted to be positioned near one or more of Bachmann's bundle, the interatrial septum, the posterior region of the right atrium, the high right atrium, the right atrial free wall along the crista terminalis, the coronary sinus, the low right atrial free wall, inside the pulmonary veins, around the pulmonary veins, the posterior-inferior region of the left atrial free wall, along the ligament of Marshall, the junctional area of the left atrial appendage and the left pulmonary veins.
 18. The system of claim 14, further comprising a sensor for receiving signals from the plurality of electrodes, wherein the processor is further operative to detect atrial tachyarrhythmia based on signals from the electrodes. 